Identification of a Mutation in FGF23 Involved in Mandibular Prognathism

Mandibular prognathism (MP) is a severe maxillofacial disorder with undetermined genetic background. We collected a Chinese pedigree with MP which involved in 23 living members of 4 generations. Genome-wide linkage analysis were carried out to obtain the information in this family and a new MP-susce...

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Bibliographic Details
Published in:Scientific reports 2015-06, Vol.5 (1), p.11250-11250, Article 11250
Main Authors: Chen, Fengshan, Li, Qin, Gu, Mingliang, Li, Xin, Yu, Jun, Zhang, Yong-Biao
Format: Article
Language:English
Subjects:
Chromosome 12
Female
Fibroblast growth factor 23
Fibroblast Growth Factors - genetics
Genomes
Humans
Linkage analysis
Male
Mandible
Mandible - abnormalities
Maxillofacial
Mutation
Pedigree
Prognathism
Prognathism - genetics
Susceptibility
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Summary:Mandibular prognathism (MP) is a severe maxillofacial disorder with undetermined genetic background. We collected a Chinese pedigree with MP which involved in 23 living members of 4 generations. Genome-wide linkage analysis were carried out to obtain the information in this family and a new MP-susceptibility locus, 12pter-p12.3 was identified. Whole-exome sequencing identified a novel heterozygous mutation in fibroblast growth factor (FGF) 23 (; p.A12D) which well segregated with MP in this pedigree within the locus. The mutation was also detected in 3 cases out of 65 sporadic MP patients, but not in any of the 342 control subjects. The p.A12D mutation may disrupt signal peptide function and inhibit secretory in FGF23. Furthermore, mutant FGF23 was overexpressed in 293T cells, increased cytoplasmic accumulation was observed compared with the wild type. We have discovered that c.35C>A mutation in FGF23 strongly associated with MP, which expand our understanding of the genetic contribution to MP pathogenesis.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep11250